Inside Story: Validating Your Sterilization Process

Many factors can affect the validation of your sterilization process, from the manufacturing environment to the chosen sterilization method and even your packaging design. To find out more about sterile product development and registration, MDB recently spoke with Elizabeth Sydnor, Director of Microbiology of Eurofins Medical Device Testing (Lancaster, PA).

MDB: How do you determine if you need sterility testing per USP <71> or ISO 11737-2?

Sydnor: USP <71> is the compendia method that is widely applicable to sterile pharmaceutical formulations, medical devices, and radiopharmaceuticals, whereas ISO 11737-2 is applicable to the validation of sterile medical devices. All sterility testing is done under the premise of USP <71>, but there are different requirements for performing the test of sterility depending on your product type and the intended use.

MDB: How long does it take for a sterilization validation to be completed?

Sydnor: There are many factors that can impact completing a sterilization validation, such as the complexity of the device, number of samples available, and the sterilization modality to name a few. However, most validations can be completed in 12 weeks from the time the product is received. This timeframe is not from the beginning of the project (design phase) to the end. This typically includes bioburden testing, sterilization cycles, sterility testing, and summary report writing.

MDB: If you find that you have high bioburden, but your sterilization process is limited, what are your recommendations for reducing bioburden?

Sydnor: It is important to collaborate with a sterility assurance group to evaluate the existing manufacturing process. A manufacturing process risk assessment would help determine the potential bioburden challenges that are at each step of the process and what could be adversely affecting the final bioburden on the device. For instance, if we were doing gamma radiation, and the process requires less than 1,000 colony forming units be on the part, then it’s important to understand what the bioburden levels are on the device throughout the manufacturing process and to determine if mitigation is necessary.

MDB: How do you define what type of cleanroom classification is needed for a product?

Sydnor: Cleanrooms are great way to manage contamination controls in critical environments (coating lines, final packaging, aseptic filling, etc.). The classification of the cleanroom will be dependent on the desired process and product. It is helpful to have a collaborative team in the early stages of development to understand the process and bioburden challenges from an end-to-end perspective. You need to understand what the microbial limits are for the sterilization method to help support and identify the risk throughout the process that could lead to higher bioburden on the product. The lower the bioburden needs to be to meet your sterilization validation requirements, the tighter the classification will be and the controls within the room.

MDB: Why is the bioburden so impactful to the sterilization validation?

Sydnor: According to ISO 11137 part 1, in order to establish the sterilization dose needed to achieve the desired sterility assurance level (SAL), a manufacturer should know the number and/or the resistance to radiation of the bioburden. A laboratory will perform a standard bioburden test to understand the naturally occurring bioburden or the microbial load of your product. The results are calculated to provide an average bioburden value, which is then used in accordance with ISO 11137-2 to calculate the minimum dose needed to achieve the desired SAL. Another approach is to use a VD _max method; however, the manufacturer must have evidence that this method can achieve the requirements for sterility. Therefore, as you can see, understanding the product bioburden is a critical component to the overall success of a sterilization validation.

MDB: How often are you required to check the classification of the cleanroom?

Sydnor: During the validation of your cleanroom, a risk assessment should be used to determine how often recertification of critical parameters are assessed. If structural changes occur or elevated bioburden is being recovered during routine testing, that could be an indication that the existing validation should be reviewed. Generally, any changes to a validated cleanroom should be assessed due to the impact this could have on your final product.

MDB: If using biological indicators (BI), should it be packed in the same packaging as the product?

Sydnor: Yes, for some sterilization validations, such as EO, part of the evaluation will be assessing the location of your BIs. An internal process challenge device (iPCD) is located within the product or product load and is representative of the product, whereas an ePCD is external to the load and is used as a control by the sterilizer during the sterilization process. An iPCD is used to get an indication of the time that it will take to achieve the desired SAL. Several factors can impact the placement and results of the BI, such as the packaging material, load configuration, and density.

To find out more about Eurofins Medical Device Testing, visit here .

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